De Bernardi B, Carli M, Casale F, Corciulo P, Cordero di Montezemolo L, De Laurentis C, Bagnulo S, Brisigotti M, Marchese N, Garaventa A
Department of Hematology-Oncology, Giannina Gaslini Children's Hospital, Genova, Italy.
J Clin Oncol. 1992 Dec;10(12):1870-8. doi: 10.1200/JCO.1992.10.12.1870.
The objective of the present study was to determine whether an increase in the intensity of therapy improves outcome for children with disseminated poor-risk neuroblastoma.
From January 1982 through November 1989, 181 children 1 year or older with newly diagnosed disseminated neuroblastoma were entered onto two consecutive studies of the Italian Cooperative Group for Neuroblastoma (ICGNB): 75 (study NB82) were enrolled from 1982 to 1984 and were treated with standard-dose (SD) chemotherapy, and 106 (study NB85) were enrolled from 1985 to 1989 and received high-dose (HD) chemotherapy. In both treatment protocols, induction therapy included peptichemio and cisplatin (at SD or HD, respectively) and removal of the primary tumor. In study NB82, children who achieved complete or partial tumor regression received SD consolidation therapy, and in study NB85 they received three cycles of HD chemotherapy (3cCT) or one cycle of myeloablative therapy (MAT) followed by autologous bone marrow transplantation (ABMT).
Compared with group NB82, the NB85 group had significantly fewer failures (no tumor response or disease progression) after administration of peptichemio (9% v 31%; P < .01), had more complete responses (CRs) and partial responses (PRs) both after treatment with cisplatin (60% v 43%; P = .01) and after surgery (76% v 57%; P < .01), and was more likely to have achieved complete excision of the primary tumor (70% v 46%; P < .01). Overall survival (OS) and progression-free survival (PFS) at 5 years were 11% and 9% in NB82, and 27% and 18% in NB85 (P < .01 for both); however, in NB85, relapses occurred even after 5 years of CR, so that PFS curves converge approximately 7 years after diagnosis. Median survival time was 14 months in NB82 and 24 months in NB85. Children in the NB85 group who after achievement of CR were consolidated with 3cCT had a 5-year PFS of 24% compared with 32% of those treated with MAT followed by ABMT (P = .5).
Intensified therapy improves response rate and prolongs survival of children with disseminated neuroblastoma, although its impact on the eventual cure rate remains to be established.
本研究的目的是确定强化治疗强度是否能改善播散性高危神经母细胞瘤患儿的预后。
1982年1月至1989年11月，181例1岁及以上新诊断为播散性神经母细胞瘤的儿童被纳入意大利神经母细胞瘤协作组（ICGNB）的两项连续研究：1982年至1984年纳入75例（研究NB82），接受标准剂量（SD）化疗；1985年至1989年纳入106例（研究NB85），接受高剂量（HD）化疗。在两种治疗方案中，诱导治疗均包括化疗药物和顺铂（分别为标准剂量或高剂量）以及切除原发肿瘤。在研究NB82中，肿瘤实现完全或部分消退的儿童接受标准剂量巩固治疗，在研究NB85中，他们接受三个周期的高剂量化疗（3cCT）或一个周期的清髓性治疗（MAT），随后进行自体骨髓移植（ABMT）。
与NB82组相比，NB85组在给予化疗药物后失败（无肿瘤反应或疾病进展）的情况明显更少（9%对31%；P<.01），在顺铂治疗后（60%对43%；P=.01）和手术后（76%对57%；P<.01）完全缓解（CR）和部分缓解（PR）的情况更多，并且更有可能实现原发肿瘤的完全切除（70%对46%；P<.01）。5年时的总生存率（OS）和无进展生存率（PFS）在NB82组分别为11%和9%，在NB85组分别为27%和18%（两者P均<.01）；然而，在NB85组中，即使在CR达到5年后仍有复发，因此PFS曲线在诊断后约7年时趋于一致。NB82组的中位生存时间为14个月，NB85组为24个月。NB85组中CR后接受3cCT巩固治疗的儿童5年PFS为24%，而接受MAT后进行ABMT治疗的儿童为32%（P=.5）。
强化治疗可提高播散性神经母细胞瘤患儿的缓解率并延长生存期，尽管其对最终治愈率的影响仍有待确定。
